Efficacy of first-line treatment with epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) alone or in combination with chemotherapy for advanced non-small cell lung cancer (NSCLC) with low-abundance mutation

Lung Cancer. 2019 Feb:128:6-12. doi: 10.1016/j.lungcan.2018.12.007. Epub 2018 Dec 6.

Abstract

Objective: The objective of this study was to investigate whether first-line treatment with epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) in combination with chemotherapy improves the prognosis of patients with advanced non-small cell lung cancer (NSCLC) who harbour low-abundance EGFR mutations.

Patients and methods: We retrospectively analysed the clinical data of 76 patients with advanced NSCLC who harboured low-abundance EGFR mutations. The patients were divided into the combination group and the monotherapy group. The combination group received EGFR-TKI combined with a platinum-based regimen. After the end of chemotherapy, EGFR-TKI was administered daily. The monotherapy group was administered EGFR-TKI therapy daily.

Results: No significant difference was observed in response rate between the different groups. The median PFS and OS were significantly longer in the combination group than in the monotherapy group (PFS: 7.9 months [95% CI,5.73-10.07] vs 5.9 months [95% CI, 4.99-6.81], p = 0.015; OS: 25.8 months[95% CI,16.27-35.33] vs 19.8 months [95% CI, 18.60-21.00], p = 0.047). Subgroup analysis showed that, for patients with the exon 21 L858R mutation, the PFS and OS were significantly longer in the combination group than in the monotherapy group (PFS: 7.2 months vs 5.8 months, p = 0.013; OS: 22.0 months vs 18.7 months, p = 0.024). The incidence of adverse events was significantly higher in the combination group.

Conclusion: For patients with advanced NSCLC and low-abundance EGFR mutations, first-line treatment with EGFR-TKI plus chemotherapy significantly improved PFS and OS. The combination therapy increased the incidence of adverse reactions, but all adverse reactions were expected and tolerated.

Keywords: EGFR; EGFR-TKI; First-Line treatment; Low-Abundance mutation; NSCLC.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / pathology
  • ErbB Receptors / genetics
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Mutation Rate
  • Mutation*
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Prognosis
  • Proportional Hazards Models
  • Protein Kinase Inhibitors / administration & dosage
  • Survival Analysis
  • Treatment Outcome

Substances

  • Protein Kinase Inhibitors
  • EGFR protein, human
  • ErbB Receptors